NA-ACIDS STIMULATES A GLUCOSE-REGULATED INSULIN-SECRETORY RESPONSE( COTRANSPORT BY METABOLIZABLE AND NONMETABOLIZABLE AMINO)

The involvement of Na+ in insulin-secretory responses to metabolizable and nonmetabolizable amino acids known to be cotransported with Na+, were examined using islet-derived BRIN-BD11 cells. At stimulatory (16. 7 mM) glucose, 10 mM of L-alanine, alpha-aminoisobutyric acid (AIB) or L-proline stimulated 1.3- to 10.4-fold (p < 0.01) insulin-secretory r esponses. In each case, these effects were significantly greater than those observed at nonstimulatory (1.1 mM) glucose (p < 0.01). While, t etrodotoxin blockade of voltage-dependent Na+ channels exerted no sign ificant effect on insulin release, Na/K pump blockade with ouabain sig nificantly promoted the amino acid-induced effects (p < 0.05), Replace ment of extracellular Na+ with equimolar N-methyl-D-glucamine(+) and o mission of extracellular K+ or Ca2+ were all effective in removing the actions of each amino acid, confirming the critical role of ionic flu xes in the secretory responses to these amino acids. Collectively thes e results demonstrate that metabolizable and nonmetabolizable amino ac ids can induce glucose-dependent insulin-secretory responses by modula ting electrogenic Na+ transport. (C) 1998 Academic Press.